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How do bacitracin, vancomycin, fosfomycin, cycloserine work?

Inhibition of cell wall synthesis

How does daptomycin work?

Unique: depolarizes bacterial membrane

How do polymixins work?

Disruption of bacterial cell membranes

Bacitracin spectrum


How is bacitracin administered?

Nephrotoxic if given systemically, so given parenterally

Most commonly topically; used intramuscularly in infants with staphylococcal infections (RARE)

Poor absorption following topical application. Marketed as ointment with polymixin B (Polysporin) or neomycin (Neosporin); often used for dermatological and ophthalmic infection

How does vancomycin work? How is it classified?

Inhibits bacterial wall synthesis by inhibiting synthesis of wall phospholipids; also inhibits peptidoglycan cross-linking

It is bactericidal glycoprotein

Spectrum of Vancomycin


Gram-positive bacteria

Indications for vancomycin


First line: infection by penicillin-resistant Strep pneumoniae
Use restricted to tx of severe infection by beta-lactam-resistant GP organisms (Strep and Staph)
Primary indication of parentral vancomyicn is endocarditis or sepsis due to MRSA

First line agent for tetanus due to clostridium tetani
Also indicated for treatment of GP infection in patient allergic to beta-lactam

How is vancomycin administered

Commonly in combination with an aminoglycoside (gentamicin) for treatment of enterococcal infection (Synergistic bactericidal effect) in beta-lactam allergic patient

Employed orally for antibiotic-associated colitis due to staph or C. defficile overgrowth

Resistance to vancomycin

Plasmid-mediated reduction in drug permeability or altered target site

Administration of vancomycin

Not absorbed orally
Treatment of systemic infection by slow I.V. infusion
Inflammation allows it to penetrate meninges
Only orally for treatment of antibiotic-induced enterocolitis

Metabolism and excretion of vancomycin

Metabolism is insignificant

Excreted by glomerular filtration, so dosage must be altered in renal insufficiency

Adverse effects of vancomycin

Fever, chills, and/or phlebitis at site of infection
Flushing and shock due to histamine released following rapid infusion

How does daptomycin work?

Bactericidal (concentration dependent killing) through depolarization of membrane potential; leads to cell death through inhibition of proteins, DNA, and RNA synthesis

Antibacterial spectrum of Daptomycin

Active against GP bacteria
Similar spectrum to vancomycin; also synergistic with aminoglycosides

Indications for daptomycin

Complicated skin and soft tissue infections, bacteremia, endocarditis

Very active against S. aureus, MRSA, VRSA
Strep pyogenes, Strep agalactiae, Enterococcus faecalis (VRE), Enterococcus faecium (VRE)

Administration, metabolism and excretion of daptomycin

Must be given by I.v.; metabolism is unclear, but it is inactivated by pulmonary surfactant; 80% excreted by glomerular filtration, so dose must be modified in renal insufficiency

Adverse effects of daptomycin

GI distrubances: constipation, nausea, diarrhea, vomiting

Headache, insomnia, dizziness
Injection site reactions and skin rashes
Abnormal liver function tests, jaundice, renal failure

Fosfomycin (monurol) mechanism

Inhibits bacterial cell walls; resistance by decreased permeability; synergistic with aminoglycosides, beta lactams, or fluroquinolones

Use of fosfomycin

GP and GN organisms; Only orally; uncomplicated UTI (acute cystitis) and is safer during pregnancy; major indication is single dose treatment of UTI in female due to E. coli or Enterococcus faecalis

Pharmacokinetics of fosfomycin

Excreted by kidneys, unchanged; diarrhea is common side effect;

Cycloserine mechanism

Inhibition of cell wall synthesis

Cycloserine use

Second-line tuberculostatic agent, since it is not more active than first-line but hase more adverse effects;

Active against many GP and GN organisms, although it isn't really used for this

Pharmacokinetics of cycloserine

Widely distributed in body fluids, including CSF; metabolized to an extent; both cycloserine and metabolite eliminated by kidneys; accumulation occurs in those with renal failure

Adverse effects of cycloserine

CNS toxicity including headaches, tremors, psychosis, convulsion; peripheral neuropathy

Polymixin B mechanism

Behave like cationic detergents; bind to and disrupt bacterial cell membranes; tey are bactericidal for several GN rods

Polymixin B spectrum

Effective against GN rods, including Pseudomonas

Spectrum also includes E. coli, Enterobacter aerogenes, H. influenzae, Klebsiella pneumoniae, Shigella; GPs, as well as Preteus, Serratia, Nisseria are resistant to polymixins

Indications for Polymixin B

Corneal ulcers and external otitis by Pseudomonas infections

Pharmacokinetics of polymixin B

Sulfate salt of polymixin B is water soluble and very stable in solution; however poorly distributed to tissues

Thus, mostly limited to topical applications in ointments with neomycin or bacitracin for superficial skin lacerations

Systemic use rare due to potential for nephrotoxicity and neurotoxicity; available for parentral use in UTI and bacteremia due to susceptible GN organisms when other antibiotics are contraindicated or ineffective

Adverse effects of Polymixin B

Major is potential for nephrotoxicity when given systemically; Neurotoxicity also associated with polymixins

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